Lattao, Ramona and Rangone, Hélène and Llamazares, Salud and Glover, David M. (2021) Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins. Developmental Cell, 56 (7). pp. 1000-1013. ISSN 1534-5807. PMCID PMC8024676. doi:10.1016/j.devcel.2021.02.019. https://resolver.caltech.edu/CaltechAUTHORS:20210318-140520845
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Abstract
Lysosome-related organelles (LROs) are endosomal compartments carrying tissue-specific proteins, which become enlarged in Chediak-Higashi syndrome (CHS) due to mutations in LYST. Here, we show that Drosophila Mauve, a counterpart of LYST, suppresses vesicle fusion events with lipid droplets (LDs) during the formation of yolk granules (YGs), the LROs of the syncytial embryo, and opposes Rab5, which promotes fusion. Mauve localizes on YGs and at spindle poles, and it co-immunoprecipitates with the LDs’ component and microtubule-associated protein Minispindles/Ch-TOG. Minispindles levels are increased at the enlarged YGs and diminished around centrosomes in mauve-derived mutant embryos. This leads to decreased microtubule nucleation from centrosomes, a defect that can be rescued by dominant-negative Rab5. Together, this reveals an unanticipated link between endosomal vesicles and centrosomes. These findings establish Mauve/LYST’s role in regulating LRO formation and centrosome behavior, a role that could account for the enlarged LROs and centrosome positioning defects at the immune synapse of CHS patients.
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| Additional Information: | © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 23 March 2020, Revised 17 November 2020, Accepted 17 February 2021, Available online 15 March 2021. We are grateful to James Mason (NIEHS), Hiro Ohkura (Edinburgh), and Jordan Raff (Oxford) for kindly providing reagents. We thank the University of Iowa DSHB, the BACPAC Resource Center (BPRC), NCI Frederick National Laboratory for Cancer Research, Coriell Institute for Medical Research and Addgene for reagents; Bloomington Drosophila Stock Center (BDSC), Drosophila Transgenesis Facility, CMB, (Spain), and the Fly Facility of the Department of Genetics (Cambridge) for fly stocks; IBB PAS (Warsaw) for mass spectrometry; and members of the Glover lab for fruitful discussion. We are grateful for grant support from Wellcome (RG84496) and NIH (R01NS119614) to D.M.G. Author contributions: R.L. designed and conducted the experiments and prepared all figures. H.R. generated the anti-Msps antibody. S.L. discovered mvros and initiated its cytological mapping and characterization of its MEL phenotype. D.M.G. supervised the project, raised funding, and wrote the manuscript with R.L. The authors declare no competing interests. | |||||||||
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| Subject Keywords: | lysosome-related organelles; centrosomes; LYST; Drosophila; mauve; minispindles/Ch-TOG; endosomal vesicle trafficking; microtubule nucleation; Chediak-Higashi syndrome | |||||||||
| Issue or Number: | 7 | |||||||||
| PubMed Central ID: | PMC8024676 | |||||||||
| DOI: | 10.1016/j.devcel.2021.02.019 | |||||||||
| Record Number: | CaltechAUTHORS:20210318-140520845 | |||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20210318-140520845 | |||||||||
| Official Citation: | Ramona Lattao, Hélène Rangone, Salud Llamazares, David M. Glover, Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins, Developmental Cell, Volume 56, Issue 7, 2021, Pages 1000-1013.e6, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2021.02.019. (https://www.sciencedirect.com/science/article/pii/S1534580721001593) | |||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
| ID Code: | 108487 | |||||||||
| Collection: | CaltechAUTHORS | |||||||||
| Deposited By: | Tony Diaz | |||||||||
| Deposited On: | 19 Mar 2021 02:15 | |||||||||
| Last Modified: | 19 Apr 2021 21:41 |
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